The Major Histocompatibility Complex (MHC) encodes molecules that provide a context for the recognition of antigen by T lymphocytes. Because of its central role in individuals' immune response, the MHC has been studied extensively by immunologists and geneticists. However, the information concerning its evolution is scant and largely limited to primates and a few rodent species. The overall goal of the proposed project is to study the MHCs of lower vertebrates by molecular cloning. The specific aims of this proposal are threefold: First, the organization of the MHC of an African clawed frog Xenopus will be studied using a recently isolated class I cDNA clone as a starting material. Second, the regulation of MHC expression in ontogeny, in particular, in metamorphosis, will be studied in various amphibian species including Xenopus and axolotl. And third, using Xenopus as a stepping stone, the MHC genes of more primitive species (shark, lamprey, and tunicates) will be isolated. Xenopus is clearly a "high connectivity" model. The information obtained from this study should further enhance its connectivity as a model organism for biomedical research. In terms of immunology, the isolation and characterization of MHC genes from primitive species should provide a clue to the primordial function of the MHC, and increase our knowledge about the evolution of immunity.